{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:34Z","timestamp":1787022214907,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013163","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2021YFD1801104"],"award-info":[{"award-number":["2021YFD1801104"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012239","name":"Hubei Technological Innovation Special Fund","doi-asserted-by":"publisher","award":["2024CSA060"],"award-info":[{"award-number":["2024CSA060"]}],"id":[{"id":"10.13039\/501100012239","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus capable of infecting various animal species, including humans. In this study, we explored the roles of sirtuins (SIRTs), a conserved family of protein deacylases and mono-adenosine diphosphate-ribosyltransferases, in PDCoV replication. Surprisingly, we found that SIRT5\u2014a unique member of SIRTs with distinct desuccinylation, demalonylation, and deglutarylation activities\u2014is a proviral factor essential for PDCoV replication; its catalytic activities are crucial in this process. Mechanistically, SIRT5 interacts with and desuccinylates the PDCoV membrane (M) protein. This modification activates the ataxia-telangiectasia mutated (ATM) pathway, facilitates ubiquitination of peroxisomal biogenesis protein 5 (PEX5), and recruits sequestosome 1 (SQSTM1\/p62) to initiate selective peroxisomal autophagy (pexophagy). The pexophagy process disrupts peroxisomal function, elevates reactive oxygen species (ROS) levels, and suppresses type I and III interferon production, thereby enhancing viral replication. We also identified lysine 207 (K207) as the primary succinylation site of the M protein. Mutations mimicking the desuccinylated or succinylated states of K207 substantially influence viral replication and the ability to induce pexophagy. These findings reveal a novel role for SIRT5 in regulating pexophagy during viral infection and suggest a therapeutic target for efforts to combat coronavirus infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013163","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T14:06:52Z","timestamp":1746799612000},"page":"e1013163","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["SIRT5-mediated desuccinylation of the porcine deltacoronavirus M protein drives pexophagy to enhance viral proliferation"],"prefix":"10.1371","volume":"21","author":[{"given":"Zhuang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puxian","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanrong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liurong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-9188","authenticated-orcid":true,"given":"Shaobo","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"issue":"22","key":"ppat.1013163.ref001","article-title":"Broad 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